The long term objectives of this work are to a) develop an understanding of the mechanisms underlying the genesis and expression of seizures; and b) to formulate a rational basis for the development of drugs to suppress the genesis and expression of seizures. The specific aims of this project are centered on the use of an in vitro model of epileptogenesis and seizure expression, using intra-and extracellular electrophysiological recordings. Rat hippocampal slices are subjected to repeated stimulus trains, resulting in the slow development of electrographic seizures (EGSs). Thus, this is an in vitro model of both seizure genesis and seizure expression. 1. Our first set of specific aims deals with the genesis of seizures. After epileptogenesis a previously innocuous stimulus will trigger a strong EGS. What changed in the network to permit the triggering of an EGS? Our past two years of work lead us to hypothesize that epileptogenesis arises from four factors: a subtle diminution of synaptic inhibition, enhanced synaptic excitation, a failure of potassium/voltage- dependent inhibitory processes, and axon terminal hyperexcitability. For this project we will concentrate on changes in potassium-sensitive processes and synaptic inhibition and excitation. 2. Our second set of specific aims deals with the triggering and expression of seizures. However a network is made seizure-prone, what physiological mechanisms actually permit the network to make the transition from interictal spiking to a tonic, and then clonic EGS; and then to slice? Because this in vitro EGS model exhibits each phase of this complex event, we can now analyze the physiological state of the network at each phase. We hypothesize that synaptic-mediated synchrony is important for the interictal-ictal transition and the clonic phase of the EGS, while non-synaptic synchrony dominates the tonic part of the EGS. For this proposal we will concentrate on the role of non synaptic (axonal) synchrony during the tonic phase of the EGS and its control by anticonvulsants.